Blood Pressure Recovery After Dobutamine Antagonism: Partial With Landiolol, None With Esmolol.

We investigated the hemodynamic effects of 2 short-acting β -blockers, landiolol and esmolol, in the continuous presence of dobutamine in a prospective, single-center, randomized, crossover study in 16 healthy White volunteers. Dobutamine was infused at a rate sufficient to increase the heart rate by at least 30 beats per minute, followed by a 60-minute infusion of 50 μg/kg/min esmolol or 10 μg/kg/min landiolol on top of the unchanged dobutamine infusion. Concentrations of β-blockers and their metabolites in blood, heart rate, and blood pressure were followed for 180 minutes.

Dobutamine Alters the Pharmacokinetic and Pharmacodynamic Behavior of Esmolol.

Background and objective This study involved an investigation into the pharmacokinetic and pharmacodynamic behavior of esmolol in the presence of dobutamine in healthy subjects of European ancestry. Methods We conducted a single-center, prospective randomized study of 16 healthy subjects with each receiving an infusion of dobutamine sufficient to increase heart rate (HR) by 30 beats per minute (bpm) followed by a 60-minute infusion of 50 µg/kg/min esmolol. Pharmacokinetics, HR, and blood pressure were evaluated for 180 minutes.

Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults.

Background: To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry.

Methods: We conducted a single-center, prospective randomized study in 16 healthy subjects each receiving an infusion of dobutamine sufficient to increase heart rate by 30 bpm followed by a 60 min infusion of 10 μg/kg/min landiolol.

Results: Dobutamine-induced increases in heart rate were stable for at least 20 min before a 60 min landiolol- infusion was started.

The dual orexin receptor antagonist daridorexant does not affect the pharmacokinetics of the BCRP substrate rosuvastatin.

Daridorexant is a dual orexin receptor antagonist in clinical development for the treatment of insomnia. Breast-cancer resistant protein (BCRP) is an efflux pump expressed in intestinal epithelium and hepatocytes, contributing to the absorption, distribution, and elimination of drugs and endogenous compounds. In vitro, daridorexant inhibits BCRP with an IC of 3.

Relative bioavailability of a pediatric dispersible tablet and adult film-coated tablet of macitentan in healthy volunteers.

To compare the pharmacokinetic (PK) properties of the pediatric dispersible tablet formulation of macitentan and the adult film-coated tablet formulation of macitentan in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover, Phase 1 study was conducted in 12 healthy adults. Subjects were randomized to one of the two possible treatment sequences A/B or B/A on Day 1 under fasted conditions.

Pharmacokinetics and Pharmacodynamics of Low-, Intermediate-, and High-Dose Landiolol and Esmolol During Long-Term Infusion in Healthy Whites.

The pharmacokinetics, pharmacodynamics, safety, and tolerability of long-term administration of esmolol and landiolol, a new fast-acting cardioselective β-blocker, were compared for the first time in Caucasian subjects in a prospective clinical trial. Twelve healthy volunteers received landiolol and esmolol by continuous infusion for 24 hours in a randomized crossover study using a dose-escalation regimen. Blood concentrations of drugs and metabolites, heart rate, blood pressure, ECG parameters, and tolerability were observed for 30 hours and compared.

Physicochemical pharmacokinetics as an optimization tool for generic development: A case study.

In spite of the fact that dissolution time profiles of 250mg ursodeoxycholic acid (UCDA) capsules developed by Sponsor and 250mg hard capsules produced by Ursofalk®, Dr. Falk Pharma GmbH, indicated similarity (f=60.6), a bioavailability study indicated unexpected differences in the formulations.

Biocomparison Study of Adult and Paediatric Dose Strengths of the Prostacyclin Receptor Agonist Selexipag.

Background And Objectives: Selexipag is an oral, non-prostanoid, selective prostacyclin receptor agonist recently marketed for the treatment of pulmonary arterial hypertension (PAH) in adults. Selexipag may also be an effective treatment in children with PAH. The aim of this study was to compare the pharmacokinetics of selexipag and its active metabolite ACT-333679 following single oral administration of one tablet of 200 µg selexipag (Treatment A) vs.

Pharmacodynamic and -kinetic Behavior of Low-, Intermediate-, and High-Dose Landiolol During Long-Term Infusion in Whites.

Pharmacokinetics, pharmacodynamics, safety, and tolerability of long-term administration of landiolol, a fast-acting cardioselective β-blocker, were investigated for the first time in white subjects in a prospective clinical trial. Blood concentrations of landiolol and its metabolites, heart rate (HR), blood pressure (BP), and electrocardiogram parameters were studied in 12 healthy volunteers receiving continuous infusions of a new 12-mg/mL formulation of landiolol using a dose-escalation regimen (10 μg/kg BW/min for 2 hours, 20 μg/kg BW/min for 2 hours, 40 μg/kg BW/min for 20 hours, 6 hours follow-up). Landiolol blood concentrations were dose proportional.

The variability of automated QRS duration measurement.

Aims: Previous studies have demonstrated substantial variability in manual assessment of QRS complex duration (QRSd). Disagreements in QRSd measurements were also found in several automated algorithms tested on digitized electrocardiogram (ECG) recordings. The aim of our study was to investigate the variability of automated QRSd measurements performed by two commercially available electrocardiographs.

Bolus application of landiolol and esmolol: comparison of the pharmacokinetic and pharmacodynamic profiles in a healthy Caucasian group.

Purpose: The aim of this prospective study was to compare in non-Asian subjects the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of two short-acting cardioselective β1-adrenergic antagonists, landiolol and esmolol, after administration of three different bolus dosages.

Materials And Methods: We conducted a single-center, prospective, double-blinded, randomized study in three cross-over periods with 12 healthy subjects (7 women and 5 men, mean age of 24.5 ± 6.

Prolonged Corrected QT Interval as a Predictor of Clinical Outcome in Acute Ischemic Stroke.

Background: This study aimed to investigate changes of corrected QT (QTc) interval during acute ischemic stroke and its correlation with high-sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP), neurological outcome, and 1-year mortality.

Methods: We registered electrocardiogram in 69 patients immediately after admission to the intensive care unit and then after 24 and 48 hours. Computed tomography was performed on admission to determine brain infarct size and localization.

Pharmacokinetics and pharmacodynamics of two different landiolol formulations in a healthy Caucasian group.

Background: To date, no data have been reported on the pharmacokinetic and pharmacodynamic properties of landiolol, a fast-acting cardioselective β1-adrenergic antagonist, in non-Asian subjects. The aim of this study was to compare two landiolol formulations in healthy Caucasian subjects.

Materials And Methods: We conducted a single-center, prospective, double-blinded, randomized study in two cross-over periods with 12 healthy subjects (7 women and 5 men) each receiving three doses (0.

Pharmacokinetics of the novel oral prostacyclin receptor agonist selexipag in subjects with hepatic or renal impairment.

Aim: The aim of the present study was to explore the effect of hepatic or renal dysfunction on the pharmacokinetics (PK), tolerability and safety of selexipag, an orally active prostacyclin receptor agonist.

Methods: Two prospective, open-label studies evaluated the PK of selexipag and its active metabolite ACT-333679 in healthy subjects and in subjects with mild, moderate and severe hepatic impairment or severe renal function impairment (SRFI). A single dose of 200 μg or 400 μg was administered.

Pharmacokinetics of the novel dual endothelin receptor antagonist macitentan in subjects with hepatic or renal impairment.

Macitentan is under development for the treatment of pulmonary arterial hypertension (PAH). Patients with PAH may suffer from comorbidities such as renal or hepatic impairment. Two prospective, single-center, open-label studies evaluated the pharmacokinetics of macitentan and its metabolites (pharmacologically active ACT-132577 and inactive ACT-373898) in healthy subjects and in subjects with mild, moderate, and severe hepatic impairment or severe renal function impairment (SRFI).

Lack of male-female differences in disposition and esterase hydrolysis of ramipril to ramiprilat in healthy volunteers after a single oral dose.

The objective of this study was to identify differences in disposition and esterase hydrolysis of ramipril between male and female volunteers. Plasma concentration and area under the concentration-time curve until the last measured concentration (AUCt) data of ramipril and its active metabolite ramiprilat (-diacid) were obtained from a randomised, cross-over bioequivalence study in 36 subjects (18 females and 18 males). Participants received a single 5-mg oral dose of two different formulations of ramipril (Formulation I and II).

Differences between lovastatin and simvastatin hydrolysis in healthy male and female volunteers:gut hydrolysis of lovastatin is twice that of simvastatin.

The aim of this pharmacokinetic evaluation was to show the effect of the extra methyl group in simvastatin on esterase hydrolysis between lovastatin and simvastatin in male and female volunteers. This study was based on the plasma concentration-time curves and the pharmacokinetics of lovastatin and simvastatin with its respective active metabolite statin-beta-hydroxy acid obtained from two different bioequivalence studies, each with 18 females and 18 males. Results were: The group of female volunteers showed a higher yield of the active metabolite beta-hydroxy acid than the group of males (p < 0.

Lack of Male-Female Differences in Disposition and Esterase Hydrolysis of Ramipril to Ramiprilat in Healthy Volunteers after a Single Oral Dose.

The objective of this study was to identify differences in disposition and esterase hydrolysis of ramipril between male and female volunteers. Plasma concentration and area under the concentration-time curve until the last measured concentration (AUCt) data of ramipril and its active metabolite ramiprilat (-diacid) were obtained from a randomised, cross-over bioequivalence study in 36 subjects (18 females and 18 males). Participants received a single 5-mg oral dose of two different formulations of ramipril (Formulation I and II).